Damage to the endothelial glycocalyx leads to endothelial dysfunction and microvascular changes, which can progress to the development cardiovascular complications. In type 2 diabetes, the... Show moreDamage to the endothelial glycocalyx leads to endothelial dysfunction and microvascular changes, which can progress to the development cardiovascular complications. In type 2 diabetes, the pathogenic diabetic milieu induces structural changes in the endothelial glycocalyx. In this thesis, we investigate if microvascular changes can be detected and used as a diagnostic marker in individuals at risk of developing cardiovascular disease. Secondly, we show that urinary MCP-1 and HPSE-1 levels are correlated with the urinary albumin creatinine ratio in a multi-ethnic cohort of individuals with type 2 diabetes. Higher urinary MCP-1 levels can be found in individuals from Moroccan and South-Asian Surinamese descent. Lastly, we show a fasting mimicking diet is effective to reduce Hba1c end BMI in South-Asian Surinamese patients with diabetes, but did not improve the microvascular health. In the diabetic glomerulus, the loss of capillaries was prevented but increased oxidative stress was found. A supplement with glycocalyx mimetic did improve the microvascular health in South-Asian individuals and showed to preserve glomerular endothelial coverage in the experimental study. In this thesis, we show that the endothelial glycocalyx can be used as a diagnostic marker for vascular health and can be used as a therapeutic target in type 2 diabetes. Show less
Lugtenberg, R.T.; Groot, S. de; Kaptein, A.A.; Fischer, M.J.; Kranenbarg, E.M.K.; Duijm-de Carpentier, M.; ... ; Dutch Breast Canc Res Grp BOOG 2020
Purpose In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness... Show morePurpose In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial. Methods 131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery. Results Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients' perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet. Conclusions FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer. Trialregister ClinicalTrials.gov Identifier: NCT02126449. Show less
